This project describes the activities of the formulation laboratory of the Pharmaceutical Resources Branch. These studies are directed toward resolving problems inherent in the intravenous delivery of antitumor agents and relate primarily to problems of inadequate water solubility and stability. Liposomes are being studied to assess their suitability to improve the stability of several poorly water soluble and unstable compounds (Spiromustine, NSC 278214, etc.). A stability indicating HPLC assay has been developed for the simultaneous determination of three intrathecal drugs: methotrexate, cytarabine and hydrocortisone sodium succinate. The stability of these agents has been evaluated in four common pharmaceutical vehicles. Several water soluble prodrugs of camptothecin have been prepared. The N,N-diethylglycine derivative was synthesized using naturally occurring camptothecin as the starting material. Antitumor data indicate activity and potency equivalent to results obtained with camptothecin.